Interaction of 3-Hydroxypicolinamide with TbIII and its Sensitizing Effect on Terbium Luminescence as a Function of pH and Medium

Coordination behaviour of 3-hydroxypicolinamide (HPA) towards TbIII is studied in aqueous and micellar media. The complex formed exists asML2 species in which HPA behaves as anO,O,N,N-chelating ligand. The solid complex is isolated from aqueous medium and characterized employing elemental analysis, TG/DTA, magnetic, IR, ESR and mass spectral data. Stability constant and other accompanying thermodynamic parameters of the TbIII complex have been determined pHmetrically. The complexation reaction is  spontaneous and exothermic. Effect of micelles andpHon the luminescence of TbIII were also studied. The emission peaks of TbIII are highly sensitized on complexation with HPA and the optimum luminescence  efficiency is obtained in slightly acidic to neutral solutions (pH 6–8). The complex decays biexponentially and the presence of ethanol and surfactants causes a large increase in the luminescence intensity protecting the complex fromradiationless deactivation processes.KEYWORDS: 3-Hydroxypicolinamide, stability constant, micelles, terbium luminescence, sensitization

A mediation approach to understanding socio-economic inequalities in maternal health-seeking behaviours in Egypt.

BACKGROUND: The levels and origins of socio-economic inequalities in health-seeking behaviours in Egypt are poorly understood. This paper assesses the levels of health-seeking behaviours related to maternal care (antenatal care [ANC] and facility delivery) and their accumulation during pregnancy and childbirth. Secondly, it explores the mechanisms underlying the association between socio-economic position (SEP) and maternal health-seeking behaviours. Thirdly, it examines the effectiveness of targeting of free public ANC and delivery care. METHODS: Data from the 2008 Demographic and Health Survey were used to capture two latent constructs of SEP: individual socio-cultural capital and household-level economic capital. These variables were entered into an adjusted mediation model, predicting twelve dimensions of maternal health-seeking; including any ANC, private ANC, first ANC visit in first trimester, regular ANC (four or more visits during pregnancy), facility delivery, and private delivery. ANC and delivery care costs were examined separately by provider type (public or private). RESULTS: While 74.2% of women with a birth in the 5-year recall period obtained any ANC and 72.4% delivered in a facility, only 48.8% obtained the complete maternal care package (timely and regular facility-based ANC as well as facility delivery) for their most recent live birth. Both socio-cultural capital and economic capital were independently positively associated with receiving any ANC and delivering in a facility. The strongest direct effect of socio-cultural capital was seen in models predicting private provider use of both ANC and delivery. Despite substantial proportions of women using public providers reporting receipt of free care (ANC: 38%, delivery: 24%), this free-of-charge public care was not effectively targeted to women with lowest economic resources. CONCLUSIONS: Socio-cultural capital is the primary mechanism leading to inequalities in maternal health-seeking in Egypt. Future studies should therefore examine the objective and perceived quality of care from different types of providers. Improvements in the targeting of free public care could help reduce the existing SEP-based inequalities in maternal care coverage in the short term

Acquisition of Chemoresistance in Gliomas Is Associated with Increased Mitochondrial Coupling and Decreased ROS Production

Temozolomide (TMZ) is an alkylating agent used for treating gliomas. Chemoresistance is a severe limitation to TMZ therapy; there is a critical need to understand the underlying mechanisms that determine tumor response to TMZ. We recently reported that chemoresistance to TMZ is related to a remodeling of the entire electron transport chain, with significant increases in the activity of complexes II/III and cytochrome c oxidase (CcO). Moreover, pharmacologic and genetic manipulation of CcO reverses chemoresistance. Therefore, to test the hypothesis that TMZ-resistance arises from tighter mitochondrial coupling and decreased production of reactive oxygen species (ROS), we have assessed mitochondrial function in TMZ-sensitive and -resistant glioma cells, and in TMZ-resistant glioblastoma multiform (GBM) xenograft lines (xenolines). Maximum ADP-stimulated (state 3) rates of mitochondrial oxygen consumption were greater in TMZ-resistant cells and xenolines, and basal respiration (state 2), proton leak (state 4), and mitochondrial ROS production were significantly lower in TMZ-resistant cells. Furthermore, TMZ-resistant cells consumed less glucose and produced less lactic acid. Chemoresistant cells were insensitive to the oxidative stress induced by TMZ and hydrogen peroxide challenges, but treatment with the oxidant L-buthionine-S,R-sulfoximine increased TMZ-dependent ROS generation and reversed chemoresistance. Importantly, treatment with the antioxidant N-acetyl-cysteine inhibited TMZ-dependent ROS generation in chemosensitive cells, preventing TMZ toxicity. Finally, we found that mitochondrial DNA-depleted cells (ρ°) were resistant to TMZ and had lower intracellular ROS levels after TMZ exposure compared with parental cells. Repopulation of ρ° cells with mitochondria restored ROS production and sensitivity to TMZ. Taken together, our results indicate that chemoresistance to TMZ is linked to tighter mitochondrial coupling and low ROS production, and suggest a novel mitochondrial ROS-dependent mechanism underlying TMZ-chemoresistance in glioma. Thus, perturbation of mitochondrial functions and changes in redox status might constitute a novel strategy for sensitizing glioma cells to therapeutic approaches

Region-Specific Expression of Mitochondrial Complex I Genes during Murine Brain Development

Mutations in the nuclear encoded subunits of mitochondrial complex I (NADH:ubiquinone oxidoreductase) may cause circumscribed cerebral lesions ranging from degeneration of the striatal and brainstem gray matter (Leigh syndrome) to leukodystrophy. We hypothesized that such pattern of regional pathology might be due to local differences in the dependence on complex I function. Using in situ hybridization we investigated the relative expression of 33 nuclear encoded complex I subunits in different brain regions of the mouse at E11.5, E17.5, P1, P11, P28 and adult (12 weeks). With respect to timing and relative intensity of complex I gene expression we found a highly variant pattern in different regions during development. High average expression levels were detected in periods of intense neurogenesis. In cerebellar Purkinje and in hippocampal CA1/CA3 pyramidal neurons we found a second even higher peak during the period of synaptogenesis and maturation. The extraordinary dependence of these structures on complex I gene expression during synaptogenesis is in accord with our recent findings that gamma oscillations – known to be associated with higher cognitive functions of the mammalian brain – strongly depend on the complex I activity. However, with the exception of the mesencephalon, we detected only average complex I expression levels in the striatum and basal ganglia, which does not explain the exquisite vulnerability of these structures in mitochondrial disorders

The provocative lumbar facet joint

Low back pain is the most common pain symptom experienced by American adults and is the second most common reason for primary care physician visits. There are many structures in the lumbar spine that can serve as pain generators and often the etiology of low back pain is multifactorial. However, the facet joint has been increasingly recognized as an important cause of low back pain. Facet joint pain can be diagnosed with local anesthetic blocks of the medial branches or of the facet joints themselves. Subsequent radiofrequency lesioning of the medial branches can provide more long-term pain relief. Despite some of the pitfalls associated with facet joint blocks, they have been shown to be valid, safe, and reliable as a diagnostic tool. Medial branch denervation has shown some promise for the sustained control of lumbar facet joint-mediated pain, but at this time, there is insufficient evidence that it is a wholly efficacious treatment option. Developing a universal algorithm for evaluating facet joint-mediated pain and standard procedural techniques may facilitate the performance of larger outcome studies. This review article provides an overview of the anatomy, pathophysiology, diagnosis, and treatment of facet joint-mediated pain

Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies

The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway

UPAYA PENURUNAN TINGKAT PENCEMARAN LIMBAH CAIR PENGOLAHAN KARET MENGGUNAKAN ZEOLIT ALAM DENGAN SISTEM BATCH

Industri pengolahan karet selain menghasilkan produk utama yaitu berupa karet remah juga menghasilkan produk sampingan berupa limbah cair. Limbah yang dihasilkan dari kegiatan tersebut berupa cairan. Limbah cair industri pengolahan karet dapat menimbulkan pencemaran lingkungan, baik pencemaran udara maupun pencemaran air. Ini dapat dilihat dari tingginya pH, BOD, COD dan amoniak yang terkandung dalam limbah tersebut. Penggunaan zeolit sebagai media adsorben dapat menurunkan tingkat cemaran limbah cair tersebut didasarkan pada sifat adsorben dan penyaring molekul dari zeolit. Tujuan penelitian ini adalah (1) Untuk menentukan daya serap zeolit dalam menurunkan pH, kadar BOD, COD, serta amoniak pada limbah cair pengolahan karet dengan diberi 3 gram, 5 gram dan 7 gram zeolit dalam 100 ml limbah, (2) Untuk mendapatkan konsentrasi penggunaan zeolit alam dalam menurunkan pH, kandungan BOD, kandungan COD, serta amoniak memenuhi kriteria mutu air untuk kebutuhan industri (Golongan C) berdasarkan Peraturan Pemerintah Nomor 82 Tahun 2001. Penelitian ini dilaksanakan di Laboratorium Teknologi Pertanian Fakultas Pertanian Universitas Bengkulu mulai bulan April sampai dengan Mei 2009. Penelitian ini, dilakukan dengan menggunakan 4 perlakuan berupa konsentrasi zeolit yaitu 0, 3, 5, dan 7 gram zeolit dalam 100 mL air limbah pengolahan karet. Masingmasing perlakuan dilakukan 3 kali pengulangan. Sehingga didapat 12 unit percobaan. Urutan pengamatan masing-masing unit percobaan dilakukan secara acak. Hasil Pengukuran pH, kadar BOD, COD, serta amoniak dan limbah cair sebelum dan sesudah adsorbsi dengan zeolit dibandingkan dengan kualitas air untuk kebutuhan industri (Golongan C) untuk mengetahui mutu air limbah, dan analisis regresi korelasi untuk mengetahui daya serap zoit serta pemakaian zeolit. Hasil uji menunjukkan penambahan konsentrasi zeolit dapat menurunkan kandungan senyawa organik pada air limbah pengolahan karet. Penambahan zeolit sebanyak, 3 gram, 5 gram, dan 7 gram dapat menurunkan nilai pH, COD, BOD dan amoniak dengan tingkat penyerapan zeolit terhadap nilai pH berturut-turut 1,48 %, 19,01 %, 21,97 %, COD berturut-turut 69,80 %, 83,79 %, dan 93,87 %, BOD berturut-turut 85 %, 91%, dan 94 %, amoniak berturut-turut 26,67 %, 55,50, dan 73,54 %. Penurunan nilai pH dari 8,10 mg/L menjadi 6,32 mg/L, COD dari 168,66 mg/L menjadi 10,33 mg/L, BOD dari 20 mg/L menjadi 1,2 mg/L masuk menjadi nilai COD dan BOD kategori air golongan C menurut Peraturan Pemerintah Nomor 82 Tahun 2001 Tentang Pengelolaan Kualitas Air Dan Pengendalian Pencemaran Air dan untuk amoniak dari 29,26 mg/L berada di bawah standar baku mutu limbah cair karet. Setelah dilakukan penelitian dan diperoleh hasil, perlu dilakukan penelitian lanjutan dengan menggunakan bahan zeolit alam dan sampel air limbah cair pengolahan karet terhadap volume limbah yang lebih besar dan menguji parameter air lainnya yang mempengaruhi kualitas limbah karet